Early stages in the biosynthesis of CNS cholesterol are to be studied. The involvement of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) in prenyl pyrophosphate pyrophosphatase (prenyl-PP-PPase) will be studied. Experiments have been designed to characterize HMG-CoA reductase and to assess changes in the enzyme's activity as a result of changing animal age, circadian rhythm or variations in diet of the animals (rats) under study. Neural prenyl PP-PPase is a soluble enzyme that, under in vitro, competes quite well with prenyl transferase for prenyl pyrophosphates. The activity of prenyl-PP-PPase results in formation of free isoprenoid alcohols which in turn are oxidized to acids. The present proposal seeks to characterize this enzyme in the CNS, and to what degree it influences cholesterol biosynthesis in the CNS. The metabolic rate of the products of this enzyme, isoprenoid alcohols, and the corresponding acids will also be studied.